The present application relates to methods and drug delivery systems for targeted drug delivery, and more particularly for ultrasonic targeted delivery using buoyancy specific drug carriers.
Drug delivery into cystic structures, such as the cerebrospinal fluid (CSF) space, specifically spinal CSF canal, urinary or gallbladder, ocular compartments, or thoracal and abdominal cavities, offers unique opportunities and challenges. High concentration of drug in the target space with good mixing leads to spectacular therapeutic results. This is seen in treatment of bacterial cystitis, where antibiotics are given systemically, e.g. intravenous or oral administration, are then concentrated by the kidney and delivered to the inflamed urinary bladder, making only a short course of antibiotics needed. In contrast, the major challenge in drug delivery to the CSF by routine systemic routes, is the existence of physiological barriers, i.e., blood brain barrier and brain liquor barrier that prevent drugs from accumulating in therapeutic concentrations at the target sites. This is evident in the case of subarachnoid hemorrhage (SAH) where blood and blood byproducts accumulate in the CSF, in the cerebral subarachnoid space and at the base of the brain causing inflammatory reactions, cerebral vasospasm, and impairment of cerebral microcirculation. The principal therapy standard is obliteration of the ruptured aneurysm by endovascular coiling or surgical clipping. However, the removal of blood, the causative agent for potentially deleterious complications, from the CSF and treatment of the effects thereof has been challenging. This is because relevant drugs mostly do not sufficiently penetrate the physiological barriers or have severe side effects when given systemically. Similarly, treatment of infectious, inflammatory, or neoplastic diseases affecting cystic structures, e.g. intraocular, intrapleural, intraperitoneal, intracholecystic, and intravesical cavities, could be safer and more efficacious when therapeutics would be given locally and distributed more effectively leading to high drug concentration at the target sites while minimizing systemic side effects. Accordingly, there is a need for methods and systems for the delivery of drugs that are not so limited.